We propose to isolate selected Connective Tissue Activating Peptides (CTAPs), and to define their chemical characteristics at a molecular level. Immunologic methods will be used to identify, localize and quantitate relevant human CTAPs in biological samples. Knowledge of the mechanisms of action of this class of regulators of connective tissue metabolism will be extended by identifying factors controlling synthesis and release of CTAPs, by defining the events occurring at the time of mediator-cell interaction, and by elucidating early consequences of activation (altered transport) as well as late events (glycosaminoglycan and proteoglycan synthesis). Relevance to rheumatic disease in man will be defined by studies of distribution and concentration of CTAPs in normal individuals and rheumatic patients, as well as by testing the therepeutic potential of selected agonists. Further, the activated human cell culture system will continue to be used as a model to test agents with potential for interdicting the inflammatory process. Our long-term objective is to sufficiently understand the mechanisms regulating connective tissue metabolism in normal man, and in degenerative and inflammatory processes, so that intelligent definitive intervention may become possible in rheumatic diseases.